Total synthesis of (-)-21 -isopentenylpaxilline

Organic Letters

Volumn 5, Issue 4, 2003, Pages 587-590

  Smith III, Amos B ^a   Cui, Haifeng ^a  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

21 ISOPENTENYLPAXILLINE; INDOLE; KETONE DERIVATIVE; PAXILLIN; UNCLASSIFIED DRUG; 21-ISOPENTENYLPAXILLINE; ALKALOID; INDOLE DERIVATIVE; INSECTICIDE;

ARTICLE; CHEMICAL BINDING; CHEMICAL STRUCTURE; HYDROGENATION; SILYLATION; STEREOCHEMISTRY; SYNTHESIS; X RAY ANALYSIS; CHEMISTRY; DEUTEROMYCETES; STEREOISOMERISM;

ALKALOIDS; INDOLES; INSECTICIDES; MITOSPORIC FUNGI; STEREOISOMERISM;

EID: 0037772315     PISSN: 15237060     EISSN: None     Source Type: Journal    
DOI: 10.1021/ol027575g     Document Type: Article

References (25)

1. Belofsky, G. N.; Gloer, J. B. Tetrahedron 1995, 51, 3959. Indole 1 is also referred to as (-)-9-prenylpaxilline.
2. For related indole-diterpene synthesis, see: (-)-paspaline (a,b), (+)-paspalicine (c,d), (+)-paspalinine (c,d) and (-)-penitrem D (e,f). (a) Smith, A. B., III; Mewshaw, R. E. J. Am. Chem. Soc. 1985, 107, 1796. (b) Mewshaw, R. E.; Taylor, M. D.; Smith, A. B., III. J. Org. Chem. 1989, 54, 3449. (c) Smith, A. B., III; Sunazuka, T.; Leenay, T. L.; Kingery-Wood, J. J. Am. Chem. Soc. 1990, 112, 8197. (d) Smith, A. B., III; Kingery-Wood, J.; Leenay, T. L.; Nolen, E. G., Jr.; Sunazuka, T. J. Am. Chem. Soc. 1992, 114, 1438. (e) Smith, A. B., III; Kanoh, N.; Minakawa, N.; Rainier, J. D.; Blase, F. R.; Hartz, R. A. Org. Lett. 1999, 1, 1263. (f) Smith, A. B., III; Kanoh, N.; Ishiyama, H. ; Hartz, R. A. J. Am. Chem. Soc. 2000, 114, 1438. (g) Smith, A. B., III; Visnick, M.; Haseltine, J. N.; Sprengeler, P. A. Tetrahedron 1986, 42, 2957.
3. For related indole-diterpene synthesis, see: (-)-paspaline (a,b), (+)-paspalicine (c,d), (+)-paspalinine (c,d) and (-)-penitrem D (e,f). (a) Smith, A. B., III; Mewshaw, R. E. J. Am. Chem. Soc. 1985, 107, 1796. (b) Mewshaw, R. E.; Taylor, M. D.; Smith, A. B., III. J. Org. Chem. 1989, 54, 3449. (c) Smith, A. B., III; Sunazuka, T.; Leenay, T. L.; Kingery-Wood, J. J. Am. Chem. Soc. 1990, 112, 8197. (d) Smith, A. B., III; Kingery-Wood, J.; Leenay, T. L.; Nolen, E. G., Jr.; Sunazuka, T. J. Am. Chem. Soc. 1992, 114, 1438. (e) Smith, A. B., III; Kanoh, N.; Minakawa, N.; Rainier, J. D.; Blase, F. R.; Hartz, R. A. Org. Lett. 1999, 1, 1263. (f) Smith, A. B., III; Kanoh, N.; Ishiyama, H. ; Hartz, R. A. J. Am. Chem. Soc. 2000, 114, 1438. (g) Smith, A. B., III; Visnick, M.; Haseltine, J. N.; Sprengeler, P. A. Tetrahedron 1986, 42, 2957.
4. For related indole-diterpene synthesis, see: (-)-paspaline (a,b), (+)-paspalicine (c,d), (+)-paspalinine (c,d) and (-)-penitrem D (e,f). (a) Smith, A. B., III; Mewshaw, R. E. J. Am. Chem. Soc. 1985, 107, 1796. (b) Mewshaw, R. E.; Taylor, M. D.; Smith, A. B., III. J. Org. Chem. 1989, 54, 3449. (c) Smith, A. B., III; Sunazuka, T.; Leenay, T. L.; Kingery-Wood, J. J. Am. Chem. Soc. 1990, 112, 8197. (d) Smith, A. B., III; Kingery-Wood, J.; Leenay, T. L.; Nolen, E. G., Jr.; Sunazuka, T. J. Am. Chem. Soc. 1992, 114, 1438. (e) Smith, A. B., III; Kanoh, N.; Minakawa, N.; Rainier, J. D.; Blase, F. R.; Hartz, R. A. Org. Lett. 1999, 1, 1263. (f) Smith, A. B., III; Kanoh, N.; Ishiyama, H. ; Hartz, R. A. J. Am. Chem. Soc. 2000, 114, 1438. (g) Smith, A. B., III; Visnick, M.; Haseltine, J. N.; Sprengeler, P. A. Tetrahedron 1986, 42, 2957.
5. For related indole-diterpene synthesis, see: (-)-paspaline (a,b), (+)-paspalicine (c,d), (+)-paspalinine (c,d) and (-)-penitrem D (e,f). (a) Smith, A. B., III; Mewshaw, R. E. J. Am. Chem. Soc. 1985, 107, 1796. (b) Mewshaw, R. E.; Taylor, M. D.; Smith, A. B., III. J. Org. Chem. 1989, 54, 3449. (c) Smith, A. B., III; Sunazuka, T.; Leenay, T. L.; Kingery-Wood, J. J. Am. Chem. Soc. 1990, 112, 8197. (d) Smith, A. B., III; Kingery-Wood, J.; Leenay, T. L.; Nolen, E. G., Jr.; Sunazuka, T. J. Am. Chem. Soc. 1992, 114, 1438. (e) Smith, A. B., III; Kanoh, N.; Minakawa, N.; Rainier, J. D.; Blase, F. R.; Hartz, R. A. Org. Lett. 1999, 1, 1263. (f) Smith, A. B., III; Kanoh, N.; Ishiyama, H. ; Hartz, R. A. J. Am. Chem. Soc. 2000, 114, 1438. (g) Smith, A. B., III; Visnick, M.; Haseltine, J. N.; Sprengeler, P. A. Tetrahedron 1986, 42, 2957.
6. For related indole-diterpene synthesis, see: (-)-paspaline (a,b), (+)-paspalicine (c,d), (+)-paspalinine (c,d) and (-)-penitrem D (e,f). (a) Smith, A. B., III; Mewshaw, R. E. J. Am. Chem. Soc. 1985, 107, 1796. (b) Mewshaw, R. E.; Taylor, M. D.; Smith, A. B., III. J. Org. Chem. 1989, 54, 3449. (c) Smith, A. B., III; Sunazuka, T.; Leenay, T. L.; Kingery-Wood, J. J. Am. Chem. Soc. 1990, 112, 8197. (d) Smith, A. B., III; Kingery-Wood, J.; Leenay, T. L.; Nolen, E. G., Jr.; Sunazuka, T. J. Am. Chem. Soc. 1992, 114, 1438. (e) Smith, A. B., III; Kanoh, N.; Minakawa, N.; Rainier, J. D.; Blase, F. R.; Hartz, R. A. Org. Lett. 1999, 1, 1263. (f) Smith, A. B., III; Kanoh, N.; Ishiyama, H. ; Hartz, R. A. J. Am. Chem. Soc. 2000, 114, 1438. (g) Smith, A. B., III; Visnick, M.; Haseltine, J. N.; Sprengeler, P. A. Tetrahedron 1986, 42, 2957.
7. For related indole-diterpene synthesis, see: (-)-paspaline (a,b), (+)-paspalicine (c,d), (+)-paspalinine (c,d) and (-)-penitrem D (e,f). (a) Smith, A. B., III; Mewshaw, R. E. J. Am. Chem. Soc. 1985, 107, 1796. (b) Mewshaw, R. E.; Taylor, M. D.; Smith, A. B., III. J. Org. Chem. 1989, 54, 3449. (c) Smith, A. B., III; Sunazuka, T.; Leenay, T. L.; Kingery-Wood, J. J. Am. Chem. Soc. 1990, 112, 8197. (d) Smith, A. B., III; Kingery-Wood, J.; Leenay, T. L.; Nolen, E. G., Jr.; Sunazuka, T. J. Am. Chem. Soc. 1992, 114, 1438. (e) Smith, A. B., III; Kanoh, N.; Minakawa, N.; Rainier, J. D.; Blase, F. R.; Hartz, R. A. Org. Lett. 1999, 1, 1263. (f) Smith, A. B., III; Kanoh, N.; Ishiyama, H. ; Hartz, R. A. J. Am. Chem. Soc. 2000, 114, 1438. (g) Smith, A. B., III; Visnick, M.; Haseltine, J. N.; Sprengeler, P. A. Tetrahedron 1986, 42, 2957.
8. For related indole-diterpene synthesis, see: (-)-paspaline (a,b), (+)-paspalicine (c,d), (+)-paspalinine (c,d) and (-)-penitrem D (e,f). (a) Smith, A. B., III; Mewshaw, R. E. J. Am. Chem. Soc. 1985, 107, 1796. (b) Mewshaw, R. E.; Taylor, M. D.; Smith, A. B., III. J. Org. Chem. 1989, 54, 3449. (c) Smith, A. B., III; Sunazuka, T.; Leenay, T. L.; Kingery-Wood, J. J. Am. Chem. Soc. 1990, 112, 8197. (d) Smith, A. B., III; Kingery-Wood, J.; Leenay, T. L.; Nolen, E. G., Jr.; Sunazuka, T. J. Am. Chem. Soc. 1992, 114, 1438. (e) Smith, A. B., III; Kanoh, N.; Minakawa, N.; Rainier, J. D.; Blase, F. R.; Hartz, R. A. Org. Lett. 1999, 1, 1263. (f) Smith, A. B., III; Kanoh, N.; Ishiyama, H. ; Hartz, R. A. J. Am. Chem. Soc. 2000, 114, 1438. (g) Smith, A. B., III; Visnick, M.; Haseltine, J. N.; Sprengeler, P. A. Tetrahedron 1986, 42, 2957.
9. Dorner, J. W.; Cole, R. J,; Cox, R. H.; Cunfer, B. M. J. Agric. Food Chem. 1984, 32, 1069-1071.
10. Smith, A. B., III; Visnick, M. Tetrahedron Lett. 1985, 26, 3757.
11. (a) Stork, G.; Benaim, J. J. Am. Chem. Soc. 1971, 93, 5938.
12. (b) Stork, G.; Benaim, J. Org. Synth. 1977, 57, 69.
13. Epoxide (+)-9 was prepared in eight steps and 22% overall yield; see Supporting Information.
14. Our initial attempt at Stork metalloenamine alkylation of the hydrazone (+)-7 with (+)-9 without the auxiliary hydrazone (+)-(8) resulted in low yield. Presumably (+)-8 is required to promote equilibration of the initially quenched kinetic anion. Considerable experimentation led to the observation that DMPU as a cosolvent was required; see Supporting Information.
15. Best results were obtained with the hydrazone (+)-7 concentration at 1 M.
16. Byproducts, comprising ca. 25% of the product mixture, which derived from both acetal and MTM ether hydrolysis, were converted to (-)-13 in two steps; see Supporting Information.
17. 3SiH significantly improved the yield.
18. Nicolaou, K. C.; Hwang, C.-K.; Nugiel, D. A. J. Am. Chem. Soc. 1989, 111, 4136.
19. NOESY NMR experiments confirmed the cis stereochemistry of pyran (-)-13.
20. There is precedent for five-membered ring closure on nitrogen instead of C-3 with MeMgBr; see: Haseltine, J. N. Ph.D. Thesis, University of Pennsylvania, 1992.
21. Kruger, C.; Rochow, E. G.; Wannagat, U. Chem. Ber. 1963, 96, 2132.
22. There is precedent for similar facile oxidations in the indole diterpene field. See ref 1 and: Ondeyka, J. G.; Helms, G. L.; Hensens, O. D.; Goets, M. A.; Zink, D. L.; Tsipouras, A.; Shoop, W. L.; Slayton, L.; Dombrowski, A. W.; Polishook, J. D.; Ostlind, D. A.; Tsou, N. N.; Ball, R. G.; Singh, S. B. J. Am. Chem. Soc. 1997, 119, 8809.
23. Attempted installation of the iodide with NIS led to decompostion.
24. Barton, D. H. R.; Kitchin, J. P.; Lester, D. J.; Motherwell, W. B.; Papoula, M. T. B. Tetrahedron 1981, 37, 73.
25. Minor amount (ca. 10%) of the over reduction product was obtained; separation was by HPLC.